Effect of heptachlor on hepatic mitochondrial oxidative phosphorylation in rat.
In a study of the hepatotoxicity of heptachlor (1,4,5,6,7,8,8-heptachlor 3a, 4,7,7 a-tetrahydro-4,7-methanoindene), a major compound of chlordane, the effect of heptachlor on the respiratory activity (oxidative phosphorylation and electron transport) of rat liver mitochondria was investigated. Heptachlor at a final concentration of 50 microM with succinate as substrate decreased the respiratory control index (RCI) due to a marked inhibition of state 3 respiration and a slight inhibition of state 4 respiration. One hundred microM heptachlor with succinate as substrate suppressed the states 3 and 4 respiration almost completely. On the other hand, heptachlor at a final concentration ranging from 50 to 100 microM with beta-hydroxybutylate (beta-HB) slightly decreased the RCI and decreased the RCI hardly at all with ascorbate plus N,N,N',N', -tetramethylphenylene diamine (TMPD) as substrate. Heptachlor at a concentration of 50 microM in the presence of succinate also decreased the ADP/O ratio of mitochondria. The mode of inhibition of succinate oxidation by heptachlor apparently is a noncompetitive inhibition, as shown by Lineweaver-Burk plot.
Meguro
T
T
Department of Public Health, Okayama University Medical School, Japan.
Izushi
F
F
Ogata
M
M
D000818:Animals; D006533:Heptachlor / Q000633:toxicity*; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D006533:Heptachlor; D010100:Oxygen